Immunology - Chapter 9 - Hypersensitivity Reactions
What are two different types of skin test
"Prick" test Intradermal test
caused by immune complex generated by Ig G that has infiltrated the tissues combing with the antigen injected intradermally
Arthus reaction
Productions of what can stimulate B-cells to selectively produce large amounts of IgE against the allergen
IL-4 and IL-13
Type I reactions are mediated by
IgE
What were two early tests that evaluated levels of components of the immune response to an allergen
Radioimmunosorbent test (RIST) Radioallergosorbent test (RAST)
How does hemolytic disease of the newborn occur?
RhD - negative mother is carrying a RhD - positive fetus During childbirth some of the fetal red blood cells leak back through the placenta into the maternal circulation if enough of these cells enter the maternal circulation the mother is "immunized" is subsequent child is also RhD - positive - "immunized" mother produces IgG against the RhD antigen
how can type IV hypersensitivity be transferred from one experimental animal by transferring
T cells sensitized to that allergen
hemolytic disease of the newborn
This disease occurs in the fetus if the fetus is Rh+ while the mother is Rh- occurs when a pregnant mother makes IgG against the red blood cells of her fetus IgG antibodies can cross the placenta
D antigen
This is what is referred to as Rh positive or Rh negative and is the most important antigen after A and B. most common antigen involved in hemolytic disease of the newborn
True/False FceRI can bind IgE without the immunoglobulin being bound to an antigen
True
Name the 4 types of hypersensitivity reactions
Type 1 - mediated by IgE (immediate hypersensitivity), mast cell degranulation Type 2 - antibody-mediated cell surface (cause cytotoxicity), complement activations Type 3 - mediated by immune complex, complement activation Type 4 - cell mediated, sensitized T cells, activated by macrophages
the immune response in Type III vs Type II reaction is to
Type III - an antigen in solution rather than on a particular cell or tissue (Type II)
Major players in Type II hypersensitivity
antibody, complement, phagocytes
the mechanism involved in type III hypersensitivity can also take place in certain forms of
autoimmunity
How do antigens stimulate an antibody-dependent immune response in Type I reactions
by causing the activation of the Th2 helper T-cell subsets
Intradermal test
carried out if results from the prick test are negative but there is still a suspicion that the individual tested may still be allergic to a particular allergen
After activation what happens to the mast cells and basophils
degranulated
Hemolytic anemias in type II hypersensitivity reactions
deposition of antibodies on the surface of red blood cells igG and IgM class activate complement and destroy the red blood cells to which they are attached certain medications and chemicals can cause reaction
Type IV can target which areas of the body
dermatitis usually initiated by small substances that get in contact with the skin and penetrate it absorbed into the skin, these molecules attach to host proteins acting as haptens forming hapten-protein complexed
How is immune complex formation damage completed in Type III reaction
due to activation of complement and recruitment of inflammatory cells inflammatory responses designed to clear immune complexes cause the tissue damage target tissues ar blood vessels walls, kidneys (glomerular basement membrane), joints and lungs
majority of the more severe clinical manifestations are due to the
early-phase response
the reactions that occur when the substances released by the mass cell have their biologic effect are called
effector phase
In extreme cases of allergic reactions what medication can be used
epinephrine
What are the two basic approaches for hypersensitivity testing
evaluating levels of components of the immune response to an allergen evaluating the actual physiological reactions of an individual to a particular allergen
What is the concept of hyposensitization
extremely small amounts of allergen are administered to an allergic individual this is repeated over a long period of time during which the amount of allergen gradually increases which eventually switches the response of the individual to the allergen from an IgE to an IgG response
serum sickness characterized by what
fever, chills, generalized rash, arthritis and sometimes kidney damage
clinical approaches to prevention of allergic reactions is
focused on decreasing symptoms rather than finding a "cure"
What are two Type II hypersensitivity diseases
goodpasture's syndrome rheumatic fever
Transfusion reactions
hemolytic reactions that can occur when large amounts of blood are transfused between individuals with incompatible blood groups
What type of hypersensitivity is a result of high circulating levels of soluble immune complexes made up of IgG or IgM Abs?
hypersensitivity III reaction
Hypersensitivity reactions
immune reactions that are overtly injurious to the host
What are symptoms of systemic anaphylaxis
increased blood vessel permeability smooth muscle contraction causes respiratory difficulties edema with severe swelling of the upper airway can lead to asphyxia cardiovascular issues
What are the two types of testing done for hemolytic disease of the newborn
indirect antiglobulin test (IAT) - test mom serum direct antiglobulin test (DAT) - test baby cells
intradermal test
injected between the different layers of the skin caution must be exercised as not to stimulate an anaphylactic reaction
Consequences of hemolytic disease of the newborn
jaundice, anemia, to fetal death
Play a major role in more chronic and often very serious manifestations of Type I hypersensitivity like chronic asthma
late-phase allergic reactions
Majority of type I reactions are
localized
Diagnostic test used to identify type IV hypersensitivity
mantoux test
Both prick test and intradermal test employ what types of controls
negative saline control positive histamine control
The clinical manifestations of localized reaction is dependent
on the anatomical site of allergen exposure and entry the amount of allergen also how deep allergen goes into the body
What are the medications that can cause hemolytic anemia - type II hypersensitivity reactions
penicillin and sulfonamides
Allergy
refers to four forms of hypersensitivity
How does the mantoux test work
replaced the tine test to test for mycobacterium tuberculosis positive test does not indicate individual has or has has tuberculosis result means individual has been exposed to mycobacterium tuberculosis (exposed to antigen)
The most common portal of entry for various allergen exposure is
respiratory tract
During the first exposure large amounts of IgE are produced these antibodies then bind to mast cells and basophils that large numbers of receptors for the Fc portion of IgE on their surfaces
sensitization phase
What are the advantages to a skin test
simple easy method very sensitive very specific to a particular allergen examines the final reaction of an individual to that allergen in vivo
What is example of the allergen test that evaluates the actual physiological reaction of an individual to a particular allergen
skin testing
"Prick" test
small amount of sample allergen is injected into the skin several different allergens can be tested positive reaction is usually indicated by the appearance in 15-30 minutes
serum sickness
systemic injury initiated by antigen-antibody complexes that circulate in the blood
Effects of both early responses and late responses tend to be localized around
the area of allergen exposure
What do the clinical manifestations observed in hypersensitivity reactions depend on
the host's response, not the nature of the antigen
The clinical manifestations of Type I reactions are a result from what
the release of either preformed or newly synthesized mediator from mast cells or basophils
Clinical appearance of dermatitis
the skin may present with redness blisters, edema, intense itching, peeling of the skin intensity of the reaction is dependent of the concentration of allergen and the degree of sensitization to the antigen duration of the reaction varis and can range from several days to several weeks after the removal of the antigen
Immediate hypersensitivity refers to
the timing between allergen exposure an the clinical manifestations of the reaction relative to the other forms of hypersensitivity reactions that take longer between exposure and clinical manifestations
Severity of transfusion reaction depends on several factors
titer of antibodies in the recipient serum (ABO high titers) the amount of blood transfused whether the recipient has been transfused wit the ABO-incompatible blood for the first time or for a subsequent time
What are clinical examples of type II reactions
transfusion reactions hemolytic anemias hemolytic disease of newborn (erythroblastosis fetus)
differences between type IV hypersensitivity and other types
type IV is mediated b CD4+ TH1 cells and CD8+ cytotoxic cells
Systemic reactions to food can range from
urticaria (hives) to systemic anaphylaxis
What are common allergens that cause anaphylaxis
venom, bee and wasp peanuts or peanut derived components certain shellfish and certain antibiotics such as penicillin
Why are some antigens allergenic
very small protein antigens on dry particles such as pollen grains become wet in the mucosa and elute proteins into it very low concentrations of proteins (often enzymes) tend to stimulate an IgE response localized to sites that are likely entry points of parasites
The most basic and self-evident method of prevention of allergic reactions is
allergen avoidance
Harmless antigens that can stimulate an IgE response are called
allergens
when an allergen comes in contact with the immune system at these sites an
allergy results
In transfusion reactions the antigens of concern in the blood transfusion are
ABO blood antigens - primary concern Rh antigens Kell and DUffy antigens
Two blood groups that have the most clinical relevance
ABO system Rh group
What is the mnemonic for the types of hypersensitivity
ACID Type 1 - *A*naphylaxis Type II - *C*ell or Surface bound Antibody Type III - *I*mmune Complex mediated Type IV - *D*elayed type hypersensitivity
True/False Foods do not cause both systemic and localized allergic reactions
False
the high affinity receptors for IgE are called
FceRI
Who developed the classification system for hypersensitivity
Gel and Coombs
Why are only certain people allergic
Genes (MHC haplotype and Th2 response) higher levels of circulating IgE
How does the approach of using antibodies against human IgE help with allergic reactions
Monoclonal anti-IgE is though to bind to IgE, thus preventing it from attaching to mast cells. In turn prevents the "arming" of the mast cells
prevention of hemolytic disease of the newborn
With RhoGAM during weeks 26-28 of pregnancy and during and after delivery; antibodies enter the maternal circulation and destroy any fetal RBCs before her immune system can respond and produce antibodies RhoGAM given to pregnant Rh- women Binds fetal agglutinogens in her blood so she will not form anti-D antibodies
The binding of antigen and subsequent cross-linking of surface FceRI by antigen binding to bound IgE is called
activation phase